Mapping the cellular response to small molecules using chemogenomic fitness signatures. Academic Article uri icon


  • Genome-wide characterization of the in vivo cellular response to perturbation is fundamental to understanding how cells survive stress. Identifying the proteins and pathways perturbed by small molecules affects biology and medicine by revealing the mechanisms of drug action. We used a yeast chemogenomics platform that quantifies the requirement for each gene for resistance to a compound in vivo to profile 3250 small molecules in a systematic and unbiased manner. We identified 317 compounds that specifically perturb the function of 121 genes and characterized the mechanism of specific compounds. Global analysis revealed that the cellular response to small molecules is limited and described by a network of 45 major chemogenomic signatures. Our results provide a resource for the discovery of functional interactions among genes, chemicals, and biological processes.

published proceedings

  • Science

altmetric score

  • 58.49

author list (cited authors)

  • Lee, A. Y., St Onge, R. P., Proctor, M. J., Wallace, I. M., Nile, A. H., Spagnuolo, P. A., ... Giaever, G.

citation count

  • 192

complete list of authors

  • Lee, Anna Y||St Onge, Robert P||Proctor, Michael J||Wallace, Iain M||Nile, Aaron H||Spagnuolo, Paul A||Jitkova, Yulia||Gronda, Marcela||Wu, Yan||Kim, Moshe K||Cheung-Ong, Kahlin||Torres, Nikko P||Spear, Eric D||Han, Mitchell KL||Schlecht, Ulrich||Suresh, Sundari||Duby, Geoffrey||Heisler, Lawrence E||Surendra, Anuradha||Fung, Eula||Urbanus, Malene L||Gebbia, Marinella||Lissina, Elena||Miranda, Molly||Chiang, Jennifer H||Aparicio, Ana Maria||Zeghouf, Mahel||Davis, Ronald W||Cherfils, Jacqueline||Boutry, Marc||Kaiser, Chris A||Cummins, Carolyn L||Trimble, William S||Brown, Grant W||Schimmer, Aaron D||Bankaitis, Vytas A||Nislow, Corey||Bader, Gary D||Giaever, Guri

publication date

  • April 2014